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PMID |
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TITLE |
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A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications. |
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ABSTRACT |
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BACKGROUND |
NlmCategory: BACKGROUND |
Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. |
METHODS |
NlmCategory: METHODS |
Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. |
RESULTS |
NlmCategory: RESULTS |
Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. No findings reached genome-wide significance (p = 8.4 × 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 × 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. |
CONCLUSIONS |
NlmCategory: CONCLUSIONS |
Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. No findings reached genome-wide significance (p = 8.4 × 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 × 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. We conclude that 1) meta-analyses of consumption data may contribute usefully to gene discovery; 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; and 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies). |
Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2010/06/29 |
revised |
2011/01/26 |
accepted |
2011/02/17 |
entrez |
2011/05/03 06:00 |
pubmed |
2011/05/03 06:00 |
medline |
2012/01/10 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Heath AC |
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Heath |
Andrew C |
AC |
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Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. aheath@wustl.edu |
Whitfield JB |
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Whitfield |
John B |
JB |
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Martin NG |
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Martin |
Nicholas G |
NG |
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Pergadia ML |
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Pergadia |
Michele L |
ML |
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Goate AM |
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Goate |
Alison M |
AM |
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Lind PA |
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Lind |
Penelope A |
PA |
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McEvoy BP |
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McEvoy |
Brian P |
BP |
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Schrage AJ |
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Schrage |
Andrew J |
AJ |
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Grant JD |
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Grant |
Julia D |
JD |
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Chou YL |
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Chou |
Yi-Ling |
YL |
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Zhu R |
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Zhu |
Rachel |
R |
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Henders AK |
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Henders |
Anjali K |
AK |
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Medland SE |
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Medland |
Sarah E |
SE |
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Gordon SD |
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Gordon |
Scott D |
SD |
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Nelson EC |
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Nelson |
Elliot C |
EC |
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Agrawal A |
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Agrawal |
Arpana |
A |
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Nyholt DR |
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Nyholt |
Dale R |
DR |
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Bucholz KK |
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Bucholz |
Kathleen K |
KK |
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Madden PA |
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Madden |
Pamela A F |
PA |
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Montgomery GW |
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Montgomery |
Grant W |
GW |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 70 |
ISSUE: 6 |
TITLE: Biological psychiatry |
ISOABBREVIATION: Biol Psychiatry |
YEAR: 2011 |
MONTH: Sep |
DAY: 15 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1873-2402 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Biol Psychiatry |
COUNTRY: United States |
ISSNLINKING: 0006-3223 |
NLMUNIQUEID: 0213264 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
CommentIn |
Biol Psychiatry. 2011 Sep 15;70(6):498-9 |
21864733 |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
DA019951 |
NIDA NIH HHS |
United States |
P60 AA011998-12 |
NIAAA NIH HHS |
United States |
R01 AA007535 |
NIAAA NIH HHS |
United States |
R01 AA007535-08 |
NIAAA NIH HHS |
United States |
R01 AA014041 |
NIAAA NIH HHS |
United States |
K05 AA017688 |
NIAAA NIH HHS |
United States |
K08 DA019951-05 |
NIDA NIH HHS |
United States |
R01 AA014041-05 |
NIAAA NIH HHS |
United States |
AA13320 |
NIAAA NIH HHS |
United States |
P60 AA011998 |
NIAAA NIH HHS |
United States |
K05 AA017688-03 |
NIAAA NIH HHS |
United States |
P50 AA011998 |
NIAAA NIH HHS |
United States |
R01 AA007728 |
NIAAA NIH HHS |
United States |
AA13321 |
NIAAA NIH HHS |
United States |
R56 DA012854 |
NIDA NIH HHS |
United States |
AA17688 |
NIAAA NIH HHS |
United States |
DA012854 |
NIDA NIH HHS |
United States |
R01 AA013321 |
NIAAA NIH HHS |
United States |
AA07728 |
NIAAA NIH HHS |
United States |
AA11998 |
NIAAA NIH HHS |
United States |
R01 DA012854 |
NIDA NIH HHS |
United States |
K08 DA019951 |
NIDA NIH HHS |
United States |
R01 DA012854-08 |
NIDA NIH HHS |
United States |
R01 AA013321-05 |
NIAAA NIH HHS |
United States |
R37 AA007728-20 |
NIAAA NIH HHS |
United States |
R01 AA013320-05 |
NIAAA NIH HHS |
United States |
R37 AA007728 |
NIAAA NIH HHS |
United States |
AA14041 |
NIAAA NIH HHS |
United States |
R01 AA013320-04 |
NIAAA NIH HHS |
United States |
R01 AA013320 |
NIAAA NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Alcohol Drinking |
genetics |
Alcoholism |
genetics |
Case-Control Studies |
genetics |
Genetic Predisposition to Disease |
genetics |
Genome-Wide Association Study |
statistics & numerical data |
Genotype |
statistics & numerical data |
Humans |
statistics & numerical data |
Phenotype |
statistics & numerical data |
Polymorphism, Single Nucleotide |
statistics & numerical data |
Quantitative Trait Loci |
genetics |
Residence Characteristics |
genetics |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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